rs11546512

chr5-163513993-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_013283.5(MAT2B):c.525A>G(p.Leu175=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,620 control chromosomes in the GnomAD database, including 16,808 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15433 hom.)
• Consequence: MAT2B NM_013283.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.1225
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2B	NM_013283.5	c.525A>G	p.Leu175=	splice_region_variant, synonymous_variant	4/7	ENST00000321757.11
MAT2B	NM_182796.2	c.492A>G	p.Leu164=	splice_region_variant, synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2B	ENST00000321757.11	c.525A>G	p.Leu175=	splice_region_variant, synonymous_variant	4/7	1	NM_013283.5	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18322 AN: 152134 Hom.: 1376 Cov.: 33

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.127 AC: 31701 AN: 248896 Hom.: 2478 AF XY: 0.133 AC XY: 17855 AN XY: 134610

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00745

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.141 AC: 205337 AN: 1458368 Hom.: 15433 Cov.: 32 AF XY: 0.142 AC XY: 102808 AN XY: 725480

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.0676

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.120 AC: 18321 AN: 152252 Hom.: 1375 Cov.: 33 AF XY: 0.122 AC XY: 9111 AN XY: 74430

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.105

Alfa AF: 0.140 Hom.: 1751

Bravo AF: 0.106

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	14
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.27
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11546512; hg19: chr5-162940999; COSMIC: COSV55200836; COSMIC: COSV55200836;